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961.
Dihydrolipoamide dehydrogenase is a common component of mammalian
multienzyme complexes that decarboxylate alpha-ketoacids and catabolize
glycine. The common function is to reoxidize a reduced lipoate component of
each complex, thereby preparing that lipoate for another round of
catalysis. Regions within dihydrolipoamide dehydrogenase involved in
association with other proteins of the complexes are poorly defined, and
despite high amino acid sequence conservation through evolution, it is
unknown if dihydrolipoamide dehydrogenases are functionally equivalent
across species. To address this issue, we asked whether the human enzyme
could restore function to the alpha-ketoacid dehydrogenase complexes in a
yeast strain deficient in endogenous dihydrolipoamide dehydrogenase. This
dihydrolipoamide dehydrogenase null mutant will not grow on non-fermentable
carbon sources. The human enzyme expressed from a CEN plasmid complemented
the growth phenotype and restored full activity to the pyruvate and
alpha-ketoglutarate dehydrogenase complexes. Human dihydrolipoamide
dehydrogenases with selected amino acid substitutions were then tested in
the null strain for their ability to restore function. Substitutions tested
represented naturally occurring candidate mutations identified in an
individual with inactive dihydrolipoamide dehydrogenase. A K37E change had
full function while a P453L change resulted in reduced dihydrolipoamide
dehydrogenase abundance in the mitochondria and no detectable catalytic
activity.
相似文献
962.
Ian M. Carr Joanne Morgan Christopher Watson Svitlana Melnik Christine P. Diggle Clare V. Logan Sally M. Harrison Graham R. Taylor Sergio D.J. Pena Alexander F. Markham Fowzan S. Alkuraya Graeme C.M. Black Manir Ali David T. Bonthron 《Human mutation》2013,34(7):945-952
Massively parallel (“next generation”) DNA sequencing (NGS) has quickly become the method of choice for seeking pathogenic mutations in rare uncharacterized monogenic diseases. Typically, before DNA sequencing, protein‐coding regions are enriched from patient genomic DNA, representing either the entire genome (“exome sequencing”) or selected mapped candidate loci. Sequence variants, identified as differences between the patient's and the human genome reference sequences, are then filtered according to various quality parameters. Changes are screened against datasets of known polymorphisms, such as dbSNP and the 1000 Genomes Project, in the effort to narrow the list of candidate causative variants. An increasing number of commercial services now offer to both generate and align NGS data to a reference genome. This potentially allows small groups with limited computing infrastructure and informatics skills to utilize this technology. However, the capability to effectively filter and assess sequence variants is still an important bottleneck in the identification of deleterious sequence variants in both research and diagnostic settings. We have developed an approach to this problem comprising a user‐friendly suite of programs that can interactively analyze, filter and screen data from enrichment‐capture NGS data. These programs (“Agile Suite”) are particularly suitable for small‐scale gene discovery or for diagnostic analysis. 相似文献
963.
964.
Functional screening and complex traits: human 21q22.2 sequences affecting learning in mice 总被引:4,自引:0,他引:4
Libraries of the mammalian genome have generally been propagated in single
cells and have been used for gene discovery through in vitro analyses. We
have expanded upon this concept by the creation of panels of YAC transgenic
mice propagating targeted megabase regions of the genome. Such a panel of
mice can be called an 'in vivo library' and genes can be identified based
on functional screens of members of the library. To test this approach, we
created a 2 Mb in vivo library of human chromosome 21q22.2. Analysis of the
library has revealed that one 570 kb YAC, in two separate founder lines,
was associated with distinct learning deficits compared with the other
21q22 YAC transgenics and non- transgenic control animals. We have
localized the gene on the YAC that causes the deficits by taking advantage
of fragmentation of the YAC during the process of microinjection. The
responsible gene is the human minibrain gene, and the homolog of the gene
in Drosophila is also associated with learning defects. These results
suggest that altered dosage of minibrain is associated with abnormal neural
development in flies and mice and, in humans, may also be involved in the
molecular pathology of Down syndrome.
相似文献
965.
966.
A basic step toward understanding skin surface temperature distributions caused by internal heat sources 总被引:2,自引:0,他引:2
This study uses numerical solutions of a bio-heat transfer equation to investigate the relationship between skin surface temperature distributions and internal heat sources under various physiological and environmental conditions. It is found that although a surface temperature distribution depends on all heat source parameters, the properly normalized distribution is primarily affected only by the depth of the heat source. This study provides a physical basis for determining the depth and type of an internal heat source from a thermogram acquired in various environmental conditions and an understanding of the basic relationship between skin surface temperature distributions and internal heat sources. 相似文献
967.
968.
Viachaslau M Barodka Edward Acheampong Garry Powell Ludmila Lobach David A Logan Zahida Parveen Valerie Armstead Muhammad Mukhtar 《Journal of translational medicine》2006,4(1):46-8
Candida albicans is a dimorphic fungus that can grow in yeast morphology or hyphal form depending on the surrounding environment. This ubiquitous
fungus is present in skin and mucus membranes as a potential pathogen that under opportunistic conditions causes a series
of systemic and superficial infections known as candidiasis, moniliasis or simply candidiasis. There has been a steady increase
in the prevalence of candidiasis that is expressed in more virulent forms of infection. Although candidiasis is commonly manifested
as mucocutaneous disease, life-threatening systemic invasion by this fungus can occur in every part of the body. The severity
of candidal infections is associated with its morphological shift such that the hyphal morphology of the fungus is most invasive.
Of importance, aberrant multiplication of Candida yeast is also associated with the pathogenesis of certain mucosal diseases. In this study, we assessed the anti-candidal
activity of the volatile anesthetic isoflurane in liquid form in comparison with the anti-fungal agent amphotericin B in an
in vitro culture system. Exposure of C. albicans to isoflurane (0.3% volume/volume and above) inhibited multiplication of yeast as well as formation of hyphae. These data
suggest development of potential topical application of isoflurane for controlling a series of cutaneous and genital infections
associated with this fungus. Elucidiation of the mechanism by which isoflurane effects fungal growth could offer therapeutic
potential for certain systemic fungal infections. 相似文献
969.
K. J. Logan J. V. Woodside I. S. Young M. C. McKinley L. Perkins-Porras† & P. P. McKeown 《Journal of human nutrition and dietetics》2010,23(1):30-37
Background: A Mediterranean diet has been shown to protect against coronary heart disease (CHD). Adherence to a Mediterranean diet can be assessed using a Mediterranean diet score. The primary aim of this pilot study was to examine whether CHD patients in a Northern European population would adopt and maintain a Mediterranean diet, with a secondary aim of comparing the effectiveness of different methodologies aimed at improving compliance.
Methods: Sixty-one patients with a diagnosis of CHD were randomised to one of three groups: either to receive conventional dietetic advice for CHD or advice to implement a Mediterranean-style diet using either behavioural counselling or nutritional counselling. Patients received a follow-up assessment at 6 months (adoption) and a subset of patients was followed up at 12 months (maintenance). The primary outcome measure was the between-group difference in the mean change in Mediterranean diet score (MDS).
Results: The change in MDS was not significantly different between groups. However, all three groups reported a significant within-group increase in MDS ( P < 0.01) at 6 and 12 months follow-up.
Conclusions: All three groups made dietary changes towards a Mediterranean diet, but behavioural counselling did not have significant additional benefit over nutritional counselling in initiating and maintaining dietary change, and neither method offering specific Mediterranean diet advice had any significant benefit in terms of improvement in MDS over conventional dietetic practice. 相似文献
Methods: Sixty-one patients with a diagnosis of CHD were randomised to one of three groups: either to receive conventional dietetic advice for CHD or advice to implement a Mediterranean-style diet using either behavioural counselling or nutritional counselling. Patients received a follow-up assessment at 6 months (adoption) and a subset of patients was followed up at 12 months (maintenance). The primary outcome measure was the between-group difference in the mean change in Mediterranean diet score (MDS).
Results: The change in MDS was not significantly different between groups. However, all three groups reported a significant within-group increase in MDS ( P < 0.01) at 6 and 12 months follow-up.
Conclusions: All three groups made dietary changes towards a Mediterranean diet, but behavioural counselling did not have significant additional benefit over nutritional counselling in initiating and maintaining dietary change, and neither method offering specific Mediterranean diet advice had any significant benefit in terms of improvement in MDS over conventional dietetic practice. 相似文献
970.
Peter McGrattan Amy Logan Mervyn Humphreys Margaret Bowers 《Medical oncology (Northwood, London, England)》2010,27(3):667-672
An 86-year-old man presented with acute hepatic failure, worsening thrombocytopenia, and anemia having been diagnosed and managed expectantly with cytogenetically normal RAEB-1. After 20 months a diagnosis of disease transformation to acute monocytic leukemia (M5b) was made. Conventional G-banded analysis of unstimulated bone marrow cultures demonstrated a jumping translocation (JT) involving proximal and distal breakpoints on donor chromosome 3 at bands 3q1?2 and 3q21, respectively. Recipient chromosomes included the long-arm telomeric regions of chromosomes 5, 10, 14, 16, and 19. A low-level trisomy 8 clone was also found in association with both proximal and distal JT clones. Conventional G-banded analysis of unstimulated peripheral blood cultures detected the proximal 3q1?2 JT clone involving recipient chromosome 10 several weeks after transformation to acute monocytic leukemia. Interestingly, JTs involving recipient chromosomes 5, 14, 16, and 19 were not detected in this peripheral blood sample. Palliative care was administered until his demise 2.2 months after disease transformation. There have been fewer than 70 cases of acquired JTs reported in the literature, including one myeloproliferative neoplasm and five acute myeloid leukemias involving a single breakpoint site on donor chromosome 3. Our case is unique as it is the first acquired case to demonstrate a JT involving alternative pericentromeric breakpoint sites on a single donor chromosome consisting of a proximal breakpoint at 3q1?2 and a more distal breakpoint at 3q21. 相似文献